Cholenergic Drugs Flashcards
acetylcholinesterase
enzyme responsible for the immediate breakdown of acetylcholine when released from the nerve ending; prevents over-stimulation of cholinergic receptor sites
Alzeheimer’s disease
degenerative disease of the cortex with loss of acetylcholine-producting cells and cholinergic receptors; characterized by progressive dementia
cholinergic agonists
responding to acetylcholine; refers to receptor sites stimulated by acetylecholine, as well as neurons that release acetylcholine
miosis
constriction of the pupil; relieves intraocular pressure in some types of glaucoma
Myasthenia gravis
autoimmune disease characterized by antibodies to cholinergic receptor sites, leading to destruction of the receptor sites and decreased response at the neuromuscular junction; it is progressive and debilitating, leading to paralysis
nerve gas
irreversible acetylcholinesterase inhibitor used in warfare to cause paralysis and death by prolonged muscle contraction and parasympathetic crisis
parasympathomimetic
mimicking the effects of the parasympathetic nervous system, leading to bradycardia, hypotension, pupil constriction, increased GI secretions and activity, increase bladder tone, relaxation of sphincters, and bronchoconstriction
bethanechol (Duvoid, Urecholine)- Prototype- Direct-Acting
PO/SQ. Treatment of nonobstructive postoperative and postpartum urinary retention, neurogenic bladder atony in adults and older children. dx and treatment of reflux esophagitis in adults, and used orally in infants and children for treatment of esophageal reflux
carbachol (Miostat) - Direct-Acting
Eye drops. Induction of miosis to treat glaucoma
cevimeline (Evoxac)- Direct-Acting
PO. Treatment of symptoms of dry mouth in Sjoegren’s
pilocarpine (Salagen)- Direct- Acting
PO. Taken with meals. Treatment of symptoms of dry mouth in pts with Sjoegren’s.
Direct-Acting Cholinergic Therapeutic Action
mimic effects of ACh and parasympathetic stimulation
Effects of Direct-Acting Cholinergic Drugs
- slowed HR
- decreased myocardial contractility
- vasodilation
- bronchoconstriction
- increased bronchial mucus secretion
- increased GI activity and secretions
- increased bladder tone
- relaxation of GI and bladder sphincters
- pupil constriction
Pharmokinetics of Direct-Acting Cholinergics
- short half-lives: 1-6 hrs
- absorbed well orally
- metabolism and excretion not known
- topical application not generally absorbed systemically
Contraindications and Cautions with Direct-Acting Cholinergics
-used sparingly due to potential undesirable systemic effects
-use with caution in the presence of any condition that would be exacerbated by parasympathetic effects:
bradycardia
hypotension
vasodilation
coronary artery disease
epilepsy
Parkinson’s
peptic ulcer
intestinal or bladder obstruction
asthma
recent GI or bladder surgery
Adverse effects of Cholinergics
CVS: bradycardia, heart block, hypotension, cardiac arrest
GI: N&V, cramps, diarrhea, increased salvation, involuntary defecation, difficulty swallowing and aspiration (r/t increased salvation), dehydration
GU: sense of urgency, sphincter relaxation
MISC: Flushing, increased diaphoresis
Clinically important Drug-Drug Interactions with Direct-Acting Cholinergics
increased risk of cholinergic effects if drugs are combined with acetylcholinesterase inhibitors
Indirect-Acting Cholinergics
drugs that react with acetylcholinesterase to prevent it from breaking down ACh in the synaptic cleft
Cholinergic Crisis
presents with progressive muscle weakness and respiratory difficulty as accumulation of ACh at the cholinergic receptor site leads to reduced impulse transmission and muscle weakness.
Ddonepezil (Aricept)- Prototype- Indirect-Acting Cholinergic
PO. Mgmt of Alzheimer’s dementia, including severe dementia
galantamine (Razadyne)- Indirect-Acting Cholinergic
PO. Mgmt of mild to moderate Alzheimer’s dementia; delays progression of dz
rivastigmine (Exelon)- Indirect-Acting Cholinergic
PO/Patch. Mgmt of mild to mod. Alzheimer’s dementia; treatment of dementia related to Parkinson dz
tacrine (Cognex)- Indirect-Acting Cholinergic
PO. Mgmt of mild. to mod. Alzheimer’s dementia; withdrawn from market in 2012
Indirect-Acting Cholinergic Therapeutic Action
reversibly block acetylcholinesterase at synaptic cleft, allows ACh to accumulate in cleft. More readily cross blood-brain barrier and seem to affect mostly cells in cortex
Pharmokinetics of Indirect-Acting Cholinergics
- well absorbed orally
- distributed throughout body
- metabolism and excretion not known
- Alzheimer’s dz meds are metabolized in liver (longterm metabolism- 70hrs)
- half-life is 1-7 hrs
Contraindications and Cautions with Indirect-Acting Cholinergics
- can induce labor and uterine contractions in pregnancy
- GI or GU obstructions
- bradycardia
- less likely to cause systemic parasympathetic effects, more localized than direct-acting, but caution should be exercised with conditions that could be exacerbated by cholinergic stimulation
Adverse Effects of Indirect-Acting Cholinergics
- Same as Direct-Acting
- CNS: H/A, blurred vision, dizziness, drowsiness
Pyridostigmine- Prototype- Indirect-Acting Cholinergic
PO/IM/IV. Treatment of myasthenia gravis, antidote for nondepolarizing neuromuscular junction blockers, increased survival after exposure to nerve gas
